The goal of this project is to examine the interactions between eosinophils and adhesive extracellular proteins occurring during transit of eosinophils from blood stream to airway and learn how the interactions relate to the alteration of eosinophil phenotype. The specific aims of this proposal are to: A) develop models of adhesion and migration of eosinophils with an emphasis on cell function; B) determine the role of integrins in models established in specific aim A; and C) determine the role of cytokines and chemokines in eosinophil-matrix interactions. To accomplish these goals, peripheral blood eosinophils will be studied in two- and three-dimensional systems of cell adhesion, spreading. and migration. The production of superoxide anion. leukotriene C4, and cytokines, e.g., GM-CSF, extent of degranulation. and cellular survival will be assessed to determine alteration of cell function after various incubations with matrix proteins (i.e. laminin isoforms). The effects of cytokines, chemokines, and anti-integrin antibodies will be examined in these assays to identify key interactions that could occur within the tissue. These observations should provide new insights into eosinophil biology and mechanisms of persistent airway damage in asthma.